National Institute of Health Dr. Ricardo Jorge
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Boletim Epidemiológico Observações: Vol. 13, Nº 36, mai-ago 2024
No full textObservações é uma publicação científica do INSA, IP, que visa contribuir para o conhecimento da saúde da população, os fatores que a influenciam, a decisão e a intervenção em Saúde Pública, assim como a avaliação do seu impacte na população portuguesa. Através do acesso público e gratuito a resultados científicos gerados por atividades de observação em saúde, monitorização e vigilância epidemiológica nas áreas de atuação do Instituto - Alimentação e Nutrição, Doenças Infeciosas, Genética Humana, Saúde Ambiental, Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Epidemiologia, Investigação em Serviços e Políticas de Saúde - é dada especial atenção à disseminação rápida de informação relevante para a resposta a temas de relevo para a saúde da população portuguesa, tendo como principal alvo todos os profissionais, investigadores e decisores intervenientes na área da Saúde Pública em Portugal.info:eu-repo/semantics/publishedVersio
Exploring flagellar contributions to motility and virulence in Arcobacter butzleri
No full textFlagella is a well-known bacterial structure crucial for motility, which also plays pivotal roles in pathogenesis. Arcobacter butzleri, an enteropathogen, possesses a distinctive polar flagellum whose functional aspects remain largely unexplored. Upon investigating the factors influencing A. butzleri motility, we uncovered that environmental conditions like temperature, oxygen levels, and nutrient availability play a significant role. Furthermore, compounds that are found in human gut, such as short-chain fatty acids, mucins and bile salts, have a role in modulating the motility, and in turn, the pathogenicity of A. butzleri. Further investigation demonstrated that A. butzleri ΔflaA mutant showed a reduction in motility with a close to null average velocity, as well as a reduction on biofilm formation. In addition, compared with the wild-type, the ΔflaA mutant showed a decreased ability to invade Caco-2 cells and to adhere to mucins. Taken together, our findings support the role of environmental conditions and gut host associated compounds influencing key physiological aspects of the gastrointestinal pathogen A. butzleri, such as motility, and support the role of the flagellum on bacterial virulence.Cristiana Mateus is recipient of a doctoral fellowship (UI/BD/151023/2021) under the scope of the CICS-UBI Programmatic Funding (UIDP/00709/2020). Susana Ferreira acknowledges UBI and FCT by the contract of Scientific Employment according to DL57/2016. The microscopy facility used in the development of this work is part of the PPBI-Portuguese Platform of BioImaging and is partially supported by the Project POCI-01-0145-FEDER-022122.. This work was supported by funds from the CICS-UBI base funding with DOI https://doi.org/10.54499/UIDB/00709/2020 (https://doi.org/10.54499/UIDB/00709/2020) and program funding with DOI https://doi.org/10.54499/UIDP/00709/2020 (https://doi.org/10.54499/UIDP/00709/2020) with national funds registered in the budget of the Foundation for Science and Technology
Sex Differences in Diagnosis, Treatment, and Cardiovascular Outcomes in Homozygous Familial Hypercholesterolemia
No full textHomozygous Familial Hypercholesterolemia International Clinical Collaborators - INSA: Mafalda Bourbon.Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by extremely increased low-density lipoprotein (LDL) cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Heterozygous familial hypercholesterolemia (HeFH) is more common than HoFH, and women with HeFH are diagnosed later and undertreated compared to men; it is unknown whether these sex differences also apply to HoFH.
Objective: To investigate sex differences in age at diagnosis, risk factors, lipid-lowering treatment, and ASCVD morbidity and mortality in patients with HoFH.
Design, setting, and participants: Sex-specific analyses for this retrospective cohort study were performed using data from the HoFH International Clinical Collaborators (HICC) registry, the largest global dataset of patients with HoFH, spanning 88 institutions across 38 countries. Patients with HoFH who were alive during or after 2010 were eligible for inclusion. Data entry occurred between February 2016 and December 2020. Data were analyzed from June 2022 to June 2023.
Main outcomes and measures: Comparison between women and men with HoFH regarding age at diagnosis, presence of risk factors, lipid-lowering treatment, prevalence, and onset and incidence of ASCVD morbidity (myocardial infarction [MI], aortic stenosis, and combined ASCVD outcomes) and mortality.
Results: Data from 389 women and 362 men with HoFH from 38 countries were included. Women and men had similar age at diagnosis (median [IQR], 13 [6-26] years vs 11 [5-27] years, respectively), untreated LDL cholesterol levels (mean [SD], 579 [203] vs 596 [186] mg/dL, respectively), and cardiovascular risk factor prevalence, except smoking (38 of 266 women [14.3%] vs 59 of 217 men [27.2%], respectively). Prevalence of MI was lower in women (31 of 389 [8.0%]) than men (59 of 362 [16.3%]), but age at first MI was similar (mean [SD], 39 [13] years in women vs 38 [13] years in men). Treated LDL cholesterol levels and lipid-lowering therapy were similar in both sexes, in particular statins (248 of 276 women [89.9%] vs 235 of 258 men [91.1%]) and lipoprotein apheresis (115 of 317 women [36.3%] vs 118 of 304 men [38.8%]). Sixteen years after HoFH diagnosis, women had statistically significant lower cumulative incidence of MI (5.0% in women vs 13.7% in men; subdistribution hazard ratio [SHR], 0.37; 95% CI, 0.21-0.66) and nonsignificantly lower all-cause mortality (3.0% in women vs 4.1% in men; HR, 0.76; 95% CI, 0.40-1.45) and cardiovascular mortality (2.6% in women vs 4.1% in men; SHR, 0.87; 95% CI, 0.44-1.75).
Conclusions and relevance: In this cohort study of individuals with known HoFH, MI was higher in men compared with women yet age at diagnosis and at first ASCVD event were similar. These findings suggest that early diagnosis and treatment are important in attenuating the excessive cardiovascular risk in both sexes.Key Points: - Question: Are there sex differences in presentation at diagnosis, management, and atherosclerotic cardiovascular diseases (ASCVD) outcomes in patients with homozygous familial hypercholesterolemia (HoFH)?; -
Findings: This cohort study of 751 patients with HoFH revealed no sex differences in age at diagnosis, treatment, and cardiovascular risk factors, except for a higher smoking prevalence in men. Men had higher incidence of myocardial infarction (MI), while other incident expressions of ASCVD morbidity were similar between sexes; - Meaning The findings indicate that HoFH represents a very high risk of premature ASCVD without clear sex differences, except a higher incidence of MI in men
Ancestry of the major long-range regulatory site of the α-globin genes in the Portuguese population with the common 3.7 kb α-thalassemia deletion
No full textBackground: The α-Major Regulatory Element (α-MRE), also known as HS-40, is located upstream of the α-globin gene cluster and has a crucial role in the long-range regulation of the α-globin gene expression. This enhancer is polymorphic and several haplotypes were identified in different populations, with haplotype D almost exclusively found in African populations. The purpose of this research was to identify the HS-40 haplotype associated with the 3.7 kb α-thalassemia deletion (-α3.7del) in the Portuguese population, and determine its ancestry and influence on patients' hematological phenotype.
Methods and results: We selected 111 Portuguese individuals previously analyzed by Gap-PCR to detect the presence of the -α3.7del: 50 without the -α3.7del, 34 heterozygous and 27 homozygous for the -α3.7del. The HS-40 region was amplified by PCR followed by Sanger sequencing. Four HS-40 haplotypes were found (A to D). The distribution of HS-40 haplotypes and genotypes are significantly different between individuals with and without the -α3.7del, being haplotype D and genotype AD the most prevalent in patients with this deletion in homozygosity. Furthermore, multiple correspondence analysis revealed that individuals without the -α3.7del are grouped with other European populations, while samples with the -α3.7del are separated from these and found more closely related to the African population.
Conclusion: This study revealed for the first time an association of the HS-40 haplotype D with the -α3.7del in the Portuguese population, and its likely African ancestry. These results may have clinical importance as in vitro analysis of haplotype D showed a decrease in its enhancer activity on α-globin gene.info:eu-repo/semantics/publishedVersio
The Impact of Sleep on Haematological Parameters in Firefighters
No full text(This article belongs to the Special Issue Shift-Work and the Individual II)Sleep is a vital process that impacts biological functions such as cell renewal, bone regeneration, and immune system support. Disrupted sleep can interrupt erythropoiesis, leading to fewer red blood cells, reduced haemoglobin concentration, and decreased haematocrit levels, potentially contributing to haematological disorders. This is particularly concerning for shift workers for example firefighters. While previous studies have explored sleep’s adverse effects on various professions, research specific to firefighters is limited. This study investigates the relationship between sleep quality and haematological parameters among firefighters in Northeast Portugal. From a sample of 201 firefighters, variations in red blood cells, haemoglobin, and haematocrit values were linked to sleep quality. The study utilised non-parametric tests (Wilcoxon-Mann-Whitney, Spearman’s correlation) to explore the connection between sleep quality and haematological profile. The impact of covariates on haematological parameters was assessed using non-parametric ANCOVA (Quade’s). A multiple regression analysis was employed to further understand how sleep quality and various confounding variables impact haematological levels. Findings suggest a negative link between sleep quality and haematological levels, meaning that as sleep quality deteriorates, there is a tendency for haematological levels to decrease, as indicated by Spearman’s correlation (rRBC = −0.157, pRBC = 0.026; rHb = −0.158, pHb = 0.025; rHCT = −0.175, pHCT = 0.013). As observed in scientific literature, the correlation found suggests a possible inhibition of erythropoiesis, the process responsible for red blood cell production. Despite firefighters presenting a haematological profile within the reference range (RBC: 5.1 × 106/mm3 (SD ± 0.4), Hb: 15.6 g/dL (SD ± 1.3), 47% (SD ± 1.0), there is already an observable trend towards lower levels. The analysis of co-variables did not reveal a significant impact of sleep quality on haematological levels. In conclusion, this study underscores the importance of sleep quality in determining haematological parameters among firefighters. Future research should investigate the underlying mechanisms and long-term implications of poor sleep quality on firefighter health. Exploring interventions to enhance sleep quality is vital for evidence-based strategies promoting firefighter well-being.This research was funded by the Portuguese Foundation for Science and Technology (FCT) through the project PCIF/SSO/0017/2018 and through National funds via FCT/MCTES (PIDDAC), CIMO (UIDB/00690/2020 and UIDP/00690/2020), and SusTEC (LA/P/0007/2020). http://doi.org/10.54499/PCIF/SSO/0017/2018
Is Nuchal Translucency of 3.0-3.4 mm an Indication for cfDNA Testing or Microarray? - A Multicenter Retrospective Clinical Cohort Study
No full textIntroduction: This study aimed to evaluate the occurrence of clinically relevant (sub)microscopic chromosomal aberrations in fetuses with the nuchal translucency (NT) range from 3.0 to 3.4 mm, which would be potentially missed by cfDNA testing.
Methods: A retrospective data analysis of 271 fetuses with NT between 3.0 and 3.4 mm and increased first trimester combined test (CT) risk in five cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed.
Results: A chromosomal aberration was identified in 18.8% fetuses (1:5; 51/271). In 15% (41/271) of cases, trisomy 21, 18, or 13 were found. In 0.7% (2/271) of cases, sex chromosome aneuploidy was found. In 1.1% (3/271) of cases, CNV >10 Mb was detected, which would potentially also be detected by genome-wide cfDNA testing. The residual risk for missing a submicroscopic chromosome aberration in the presented cohorts is 1.8% (1:54; 5/271).
Conclusion: Our results indicate that a significant number of fetuses with increased CT risk and presenting NT of 3.0-3.4 mm carry a clinically relevant chromosomal abnormality other than common trisomy. Invasive testing should be offered, and counseling on NIPT should include the test limitations that may result in NIPT false-negative results in a substantial percentage of fetuses
Impacte direto e indireto da Pandemia COVID-19 na mortalidade por todas as causas e por causas específicas em Portugal entre março de 2020 e dezembro de 2021
No full textPrémio Ricardo Jorge de Saúde Pública, 2024 - Menção HonrosaIntrodução:
Durante a pandemia de COVID-19 foram observados excessos de mortalidade muito elevados e muito superiores aos observados no período pré-pandemia. No entanto, é menor a evidência sobre o impacte direto (devido à infeção e suas complicações) e indireto (em consequência das medidas não farmacológicas e das alterações no acesso e procura de cuidados de saúde). Este trabalho teve como objetivo colmatar essa lacuna do conhecimento, e pretendeu: i) estimar o excesso de mortalidade por todas as causas e por causas específicas; ii) estimar o impacte direto e indireto da COVID-19.
Material e Métodos:
Foi realizado um estudo quasi-experimental de séries temporais no qual se estimou o excesso de mortalidade por todas as causas e por causas específicas, como a diferença entre a mortalidade observada e esperada tendo em conta condições atmosféricas (temperaturas, poluição atmosférica) e epidemiológicas (incidência de gripe). Numa segunda fase foram considerados os efeitos diretos da COVID-19 (mortalidade por COVID-19) e efeitos indiretos da COVID-19 (Índice de Contingência; ocupação hospitalar por COVID-19) para estimar a fração do excesso de mortalidade diretamente atribuível à COVID-19.
Resultados:
Foram estimados 21 243 (204 por 100 000) óbitos em excesso por todas as causas, 90 % dos quais foram diretamente atribuíveis à COVID-19. Ainda na mortalidade por todas as causas, estimaram-se excessos significativos nos grupos etários acima dos 65 anos de idade e nas regiões do Norte até ao Alentejo. Observou-se um aumento do excesso de mortalidade com a idade (2 924 óbitos em excesso por 100 000 no grupo etário ≥ 85 anos) e um aumento crescente de norte para sul (174 por 100 000 no Norte a 413 por 100 000 no Alentejo). Quanto ao impacto direto da COVID-19, este variou inversamente com a idade (95 % entre os 65-74 anos até 85 % ≥ 85 anos) e entre regiões (63 % no Alentejo a 83 % no Centro).
Foram estimados 187 óbitos em excesso por 100 000 nas causas respiratórias, 98 % dos quais diretamente atribuíveis à COVID-19 e 18 óbitos em excesso por 100 000 nas causas acidentais. O aumento das mortes por causas acidentais ocorreu em períodos de menor intensidade das medidas restritivas. Foi ainda observado um aumento nas causas de mortes mal-definidas ou desconhecidas, que parece maioritariamente associado ao efeito direto da COVID-19 (69 %). Nas restantes causas de morte estudadas não foram identificados excessos de mortalidade para todo o período. Contudo, no primeiro ano da pandemia observou-se um aumento da mortalidade, em períodos específicos, de várias causas de morte, seguido de uma diminuição da mortalidade abaixo da linha de base após fevereiro de 2021. Esta evolução temporal não é habitual e deverá ser analisada em estudos específicos para identificação dos mecanismos subjacentes.
Conclusão:
A pandemia de COVID-19 teve um impacte de muito elevada intensidade na mortalidade, principalmente devido às mortes por COVID-19. Estes impactes não foram iguais para toda a população, tendo sido mais intensos nos grupos etários mais idosos e nos indivíduos com doenças crónicas. Tal reforça a necessidade de dar prioridade a estes grupos populacionais na preparação e resposta a futuras pandemias, quer na proteção em relação à infeção e suas complicações, quer na prevenção e mitigação dos efeitos secundários das medidas não farmacológicas.N/
Alkyl deoxyglycoside-polymyxin combinations against critical priority carbapenem-resistant gram-negative bacteria
No full textThe escalating antimicrobial resistance crisis urges the development of new antibacterial treatments with innovative mechanisms of action, particularly against the critical priority carbapenem-resistant Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA) and Enterobacteriaceae (CRE). Membrane-disrupting dodecyl deoxyglycosides have been reported for their interesting phosphatidylethanolamine-associated bactericidal activity against Gram-positive strains; however, their inability to penetrate the Gram-negative outer membrane (OM) renders them useless against the most challenging pathogens. Aiming to repurpose alkyl deoxyglycosides against Gram-negative bacteria, this study investigates the antimicrobial effects of five reference compounds with different deoxygenation patterns or anomeric configurations in combination with polymyxins as adjuvants for enhanced OM permeability. The generation of the lead 4,6-dideoxy scaffold was optimized through a simultaneous dideoxygenation step and applied to the synthesis of a novel alkyl 4,6-dideoxy C-glycoside 5, herein reported for the first time. When combined with subtherapeutic colistin concentrations, most glycosides demonstrated potent antimicrobial activity against several multidrug-resistant clinical isolates of CRAB, CRE and CRPA exhibiting distinct carbapenem resistance mechanisms, together with acceptable cytotoxicity against human HEK-293T and Caco-2 cells. The novel 4,6-dideoxy C-glycoside 5 emerged as the most promising prototype structure for further development (MIC 3.1 μg/mL when combined with colistin 0.5 μg/mL against CRPA or 0.25 μg/mL against several CRE and CRAB strains), highlighting the potential of C-glycosylation for an improved bioactive profile. This study is the first to show the potential of IM-targeting carbohydrate-based compounds for the treatment of infections caused by MDR Gram-negative pathogens of clinical importance.This work was funded by FCT/MCTES (UIDB/00100/2020, LA/P/0056/2020 and UIDB/00211/2020) through national funds. A.M.M. also thanks FCT for funding through the Individual Call for Scientific Employment Stimulus (2022.07037.CEECIND)
Occupational second-hand smoke exposure: A comparative shotgun proteomics study on nasal epithelia from healthy restaurant workers
No full textComparative StudyNon-smokers exposed to second-hand smoke (SHS) present risk of developing tobacco smoke-associated pathologies. To investigate the airway molecular response to SHS exposure that could be used in health risk assessment, comparative shotgun proteomics was performed on nasal epithelium from a group of healthy restaurant workers, non-smokers (never and former) exposed and not exposed to SHS in the workplace. HIF1α-glycolytic targets (GAPDH, TPI) and proteins related to xenobiotic metabolism, cell proliferation and differentiation leading to cancer (ADH1C, TUBB4B, EEF2) showed significant modulation in non-smokers exposed. In never smokers exposed, enrichment of glutathione metabolism pathway and EEF2-regulating protein synthesis in genotoxic response were increased, while in former smokers exposed, proteins (LYZ, ATP1A1, SERPINB3) associated with tissue damage/regeneration, apoptosis inhibition and inflammation that may lead to asthma, COPD or cancer, were upregulated. The identified proteins are potential response and susceptibility/risk biomarkers for SHS exposure.Highlights: - Nasal airway epithelium is a valid tissue in the assessment of SHS-induced molecular changes; - HIF1α-glycolytic targets induced in cancer showed significant modulation in NSE; - NE may activate GSH metabolism and EEF2 – regulation in response to genotoxic stress; - FE may be at high risk for Serpin B3-associated diseases (lung cancer, asthma, COPD).This work was supported by the Calouste Gulbenkian Foundation, Portuguese Central Administration of Nacional Health System, the Portuguese Rede Nacional de Espectrometria de Massa, the National Institute of Health Doctor Ricardo Jorge, and the Centre for Toxicogenomics and Human Health – ToxOmics from NOVA Medical School-FCM, UNL. SN and SP were granted with PhD fellowships from Portuguese Fundação para a Ciência e a Tecnologia
Mark–Release–Recapture Trial with Aedes albopictus (Diptera, Culicidae) Irradiated Males: Population Parameters and Climatic Factors
No full textThis article belongs to the Special Issue Insect Vectors of Human and Zoonotic DiseasesAedes albopictus is considered one of the major invasive species in the world and can transmit viruses such as dengue, Zika, or chikungunya. The Sterile Insect Technique (SIT) can be used to suppress the native populations of Ae. albopictus. Mark–release–recapture (MRR) studies are crucial to support the development of the release strategy during the SIT application. Meanwhile, weather conditions can affect the MRR trial’s results and it is critical to understand the influence of climatic factors on the results. In October 2022, 84,000 irradiated sterile males were released for three consecutive weeks in Faro, Southern Portugal. Mosquitoes were recaptured by human landing collection (HLC) one, two, four, and six days after release. Generalized linear models with a negative binomial family and log function were used to estimate the factors associated with the number of recaptured mosquitoes, prevalence ratios, and the 95% confidence intervals (CIs). A total of 84,000 sterile male mosquitoes were released, with 528 recaptured (0.8%) by HLC. The prevalence of recaptured mosquitoes was 23% lower when the wind intensity was moderate. Marked sterile males had an average median distance travelled of 88.7 m. The median probability of daily survival and the average life expectancy were 61.6% and 2.1 days, respectively. The wild male population estimate was 443.33 males/ha. Despite no statistically significant association being found with humidity, temperature, and precipitation, it is important to consider weather conditions during MRR trial analyses to obtain the best determinant estimation and a more efficient application of the SIT in an integrated vector management program.Simple Summary: Aedes albopictus mosquitoes spread arboviruses like dengue, Zika, or chikungunya. The Sterile Insect Technique (SIT) can be used as a prevention and control tool against Ae. albopictus populations. Mark–release–recapture (MRR) trials are fundamental to estimate the size of the wild population in target areas and to determine the dispersal capacity and survival of sterile males in open field conditions. Environmental conditions can affect the MRR trial’s results; thus, the influence of climatic factors on the first MRR trial with Ae. albopictus marked sterile males conducted in Portugal was analyzed. In October 2022, for three consecutive weeks at two different release points, 84,000 sterile males were released over 50 ha of the study area, in the municipality of Faro, Southern Portugal, and mosquitoes were recaptured by human landing collection (HLC) one, two, four, and six days after release. Distance travelled, daily survival, and life expectancy in the field were estimated for the released sterile males and the influence of climatic factors was analyzed. Despite no statistically significant association being found with humidity, temperature, and precipitation, it is crucial to plan MRRs, considering weather conditions for a more efficient application of the SIT in an integrated vector management program.The main research and the APC were technically supported and funded by the International Atomic Energy Agency under the National Technical Cooperation Project with the reference POR5006—Integrating the Sterile Insect Technique (SIT) in the Control of the Invasive Vector Mosquito Aedes albopictus in Portugal. The study has also been partially supported by Fundação para a Ciência e Tecnologia (FCT), I.P. grant number CEECINST/00049/2021/CP2817/CT0001.info:eu-repo/semantics/publishedVersio